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Diabetic peripheral neuropathy (DPN) is caused by several factors, including reactive free oxygen radicals (ROS)-induced excessive Ca2+ influx. Transient receptor potential (TRP) vanilloid 4 (TRPV4) is a member of the Ca2+-permeable TRP superfamily. Resveratrol (RESV) has been extensively utilized in TRP channel regulation due to its pharmacological properties, which include antioxidant and TRP inhibitory effects. The protective function of RESV and the contribution of TRPV4 to streptozotocin (STZ)-induced neuropathic pain in mice are still unclear. Here, we evaluated the effects of RESV through the modulation of TRPV4 on Ca2+ influx, ROS-mediated pain, apoptosis, and oxidative damage in the mouse dorsal root ganglion (DRGs). From the 32 mice, four groups were induced: control, RESV, STZ, and STZ + RESV. We found that the injection of RESV reduced the changes caused by the STZ-induced stimulation of TRPV4, which in turn increased mechanical/thermal neuropathic pain, cytosolic Ca2+ influx, TRPV4 current density, oxidants (lipid peroxidation, mitochondrial ROS, and cytosolic ROS), and apoptotic markers (caspase-3, -8, and -9). The RESV injection also increased the STZ-mediated reduction of viability of DRG and the amounts of glutathione, glutathione peroxidase, vitamin A, β-carotene, and vitamin E in the brain, erythrocytes, plasma, liver, and kidney. All of these findings suggest that TRPV4 stimulation generates oxidative neurotoxicity, neuropathic pain, and apoptosis in the STZ-induced diabetic mice. On the other hand, neurotoxicity and apoptosis were reduced due to the downregulation of TRPV4 carried out through the RESV injection. An overview of how resveratrol (RESV) inhibits TRPV4 in mice to modulate the effects of diabetes mellitus-induced diabetic peripheral neuropathy (DPN). Ruthenium red (RuR) inhibits TRPV4, while GSK1016790A (GSK) and reactive free oxygen radicals (ROS) activate it. In the mitochondria of DRGs, the glucose oxidation brought on by diabetes mellitus (STZ) causes an intracellular free Ca2+ and Zn2+ influx excess that is dependent on TRPV4. The administration of STZ leads to the DRG becoming more depolarized (ΔΨm), which in turn causes an increase in mitochondrial ROS, apoptosis, and caspases (caspase-3, caspase-8, and caspase-9) by downregulating enzymatic (glutathione peroxidase, GSH-Px) and non-enzymatic (glutathione (GSH), vitamin A, and vitamin E) antioxidants. The mice's molecular pathways were diminished by the RESV injections. (Increase (↑); diminish (↓)) [ABSTRACT FROM AUTHOR]

Carnation (Dianthus caryophyllus L.) plant is native to the Mediterranean region. However, it is cultivated throughout the world for its beautiful flowers. In Pakistan, its flower yield and quality is very poor due to numerous abiotic stresses including salt stress, which drastically decreases plant growth, flower yield and quality. The aim of the present study was to evaluate foliar application of moringa and mint leaf extracts (0.03% each, separately) to mitigate negative effects of irrigation water salinity (0, 30 and 60 mM NaCl) on carnation plants. Salinity treatments reduced plant height, plant fresh and dry weights, leaf number, root length, number of flower buds, number of flowers, fresh and dry weights of flowers, photosynthetic pigments, i.e. chlorophyll a, chlorophyll b and total chlorophyll, and carotenoid content as well as ascorbic acid content. However, number of branches increased at 30 mM irrigation water salinity level and then decreased at 60 mM, while hydrogen peroxide (H2O2), malondialdehyde (MDA), peroxidase (POD) and catalase (CAT) activities increased with an increase in salinity level. Leaf length, root fresh weight, total phenolic content and superoxide dismutase (SOD) activity in leaves remained unaffected due to the salinity treatments. Over all, performance of mint leaf extract was better that of moringa; however, moringa leaf extract was more effective in improving leaf carotenoids content than mint leaf extract. Both, extracts reduced H2O2 and MDA contents. Leaf length, root length, root fresh weight, fresh weight of flowers and total phenolic content remained unaffected due to foliar application of extracts. Present study revealed that plant extracts especially mint leaf extract had good potential to mitigate negative effects of salt stress in carnation through regulation of metabolic and biochemical capabilities. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression. Methods and results: The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4's protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions. Conclusion: P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved. [ABSTRACT FROM AUTHOR]

This study investigated the effect of captopril (Cap) on spinal cord ischemia-reperfusion injury (SCII) in rats. Twenty-four adults male Wistar rats were randomly divided into four groups of six animals each: spinal cord ischemia-reperfusion (SCI-R) with Cap (SCI-R + Cap), SCI-R, shamoperated with Cap (SHAM + Cap), and SHAM. The 24 hr and 90 min before ischemia induction, Cap was administered intragastrically (100 mg kg-1) to the SHAM + Cap and SCI-R + Cap groups. Abdominal aortic clamping was performed in the SCI-R and SCI-R + Cap groups for 40 min. Hindlimb motor function was evaluated using the Tarlov Scale at 4, 6, 12, 24, 48, and 60 hr after SCII. The malondialdehyde (MDA), the ferric-reducing ability of plasma (FRAP) and prooxidantantioxidant balance (PAB) values were also measured. Throughout the study period, the SCI-R group had significantly lower motor function scores compared to the other groups. The MDA and PAB levels were higher and the FRAP value was lower in the SCI-R group compared to in the SHAM group. The SCI-R + Cap had higher motor function scores compared to the SCI-R group at all time points. There were no significant differences in MDA concentration, FRAP and PAB values between the SCI-R + Cap and SCI-R groups. Captopril may act as a protective agent against SCII in rats based on hind limb motor function assessment. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression. Methods and results The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4’s protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions. Conclusion P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.

Background: Cochlear hair cell injury is a common pathological feature of hearing loss. The basic helix-loophelix family, member e40 (Bhlhe40), a gene belonging to the basic helix-loop-helix (bHLH) family, exhibits strong transcriptional repression activity. Methods: Oxidative damage, in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, was caused using hydrogen peroxide (H2O2). The Ad-Bhlhe40 particles were constructed to overexpress Bhlhe40 in HEI-OC1 cells. Various assays including cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferasemediated dUTP nick end-labeling assay (TUNEL), flow cytometry, immunofluorescence, and corresponding commercial kits were employed to investigate the impacts of Bhlhe40 on cell viability, apoptosis, oxidative stress levels, mitochondrial membrane potential and cellular senescence. Additionally, a dual-luciferase reporter assay was performed to confirm the targeting of the histone deacetylases 2 (Hdac2) by Bhlhe40. Results: The results revealed that Bhlhe40 was downregulated in H2O2-treated HEI-OC1 cells, but its overexpression improved cell viability and mitigated H2O2-induced oxidative injury in HEI-OC1 cells with increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities and decrease of reactive oxygen species (ROS) levels. Besides, overexpression of Bhlhe40 suppressed H2O2-triggered cell senescence, as evidenced by the fact that the upregulation of P53, P21, and P16 in HEI-OC1 cells treated with H2O2 were all alleviated by Bhlhe40 overexpression. And we further verified that overexpression of Bhlhe40 could inhibit the expression of Hdac2, which may be related to the repression of Hdac2 transcription. Conclusion: This study suggests that Bhlhe40 plays a protective role against senescence and oxidative damage in cochlear hair cells exposed to H2O2. [ABSTRACT FROM AUTHOR]

Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor H2O2 evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new "green" carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations. [ABSTRACT FROM AUTHOR]

Simple Summary: The small intestine of ruminants is an important organ in the digestion and absorption of rumen indigestible nutrients while it is prone to oxidative stress, causing barrier damage, thus intestinal absorption and metabolic disorders. Nicotinamide was previously found to have antioxidant properties. The aims of this study were to investigate the effect of nicotinamide on intestinal oxidative damage and explore its potential mechanism. The study revealed that nicotinamide effectively reduced oxidative damage in bovine intestinal epithelial cells through autophagy. This protective effect was evidenced by enhanced antioxidant capacity and increased expression of tight junction proteins, suggesting nicotinamide's role in improving cellular defense and intestinal barrier integrity. The small intestine is important to the digestion and absorption of rumen undegradable nutrients, as well as the barrier functionality and immunological responses in ruminants. Oxidative stress induces a spectrum of pathophysiological symptoms and nutritional deficits, causing various gastrointestinal ailments. Previous studies have shown that nicotinamide (NAM) has antioxidant properties, but the potential mechanism has not been elucidated. The aim of this study was to explore the effects of NAM on hydrogen peroxide (H2O2)-induced oxidative injury in bovine intestinal epithelial cells (BIECs) and its potential mechanism. The results showed that NAM increased the cell viability and total antioxidant capacity (T-AOC) and decreased the release of lactate dehydrogenase (LDH) in BIECs challenged by H2O2. The NAM exhibited increased expression of catalase, superoxide dismutase 2, and tight junction proteins. The expression of autophagy-related proteins was increased in BIECs challenged by H2O2, and NAM significantly decreased the expression of autophagy-related proteins. When an autophagy-specific inhibitor was used, the oxidative injury in BIECs was not alleviated by NAM, and the T-AOC and the release of LDH were not affected. Collectively, these results indicated that NAM could alleviate oxidative injury in BIECs by enhancing antioxidant capacity and increasing the expression of tight junction proteins, and autophagy played a crucial role in the alleviation. [ABSTRACT FROM AUTHOR]

Aims: Putative beneficial effects of neuropeptide W (NPW) in the early phase of gastric ulcer healing process and the involvement of cyclooxygenase (COX) enzymes were investigated in an acetic acid-induced gastric ulcer model. Main methods: In anesthetized male Sprague–Dawley rats, acetic acid was applied surgically on the serosa and then a COX-inhibitor (COX-2-selective NS-398, COX-1-selective ketorolac, or non-selective indomethacin; 2 mg/kg/day, 3 mg/kg/day or 5 mg/kg/day; respectively) or saline was injected intraperitoneally. One h after ulcer induction, omeprazole (20 mg/kg/day), NPW (0.1 μg/kg/day) or saline was intraperitoneally administered. Injections of NPW, COX-inhibitors, omeprazole or saline were continued for the following 2 days until rats were decapitated at the end of the third day. Key findings: NPW treatment depressed gastric prostaglandin (PG) I2 level, but not PGE2 level. Similar to omeprazole, NPW treatment significantly reduced gastric and serum tumor necrosis factor-alpha and interleukin-1 beta levels and depressed the upregulation of nuclear factor kappa B (NF-κB) and COX-2 expressions due to ulcer. In parallel with the histopathological findings, treatment with NPW suppressed ulcer-induced increases in myeloperoxidase activity and malondialdehyde level and replenished glutathione level. However, the inhibitory effect of NPW on myeloperoxidase activity and NPW-induced increase in glutathione were not observed in the presence of COX-1 inhibitor ketorolac or the non-selective COX-inhibitor indomethacin. Significance: In conclusion, NPW facilitated the healing of gastric injury in rats via the inhibition of pro-inflammatory cytokine production, oxidative stress and neutrophil infiltration as well as the downregulation of COX-2 protein and NF-κB gene expressions. [ABSTRACT FROM AUTHOR]

Atherosclerosis constitutes a proverbial pathogenic mechanism for cardio-cerebrovascular disease that accounts for the most common cause of disability and morbidity for human health worldwide. Endothelial dysfunction and inflammation are the key contributors to the progression of atherosclerosis. Glutaredoxin 2 (GLRX2) is abundantly existed in various tissues and possesses a range of pleiotropic efficacy including anti-oxidative and anti-inflammatory responses. However, its role in atherosclerosis is still undefined. Here, down-regulation of GLRX2 was validated in lipopolysaccha (LPS)-induced vascular endothelial cells (HUVECs). Moreover, elevation of GLRX2 reversed the inhibition of cell viability in LPS-treated HUVECs and decreased LPS-induced increases in cell apoptosis and caspase-3 activity. Additionally, enhancement of GLRX2 expression antagonized oxidative stress in HUVECs under LPS exposure by inhibiting ROS, lactate dehydrogenase and malondialdehyde production and increased activity of anti-oxidative stress superoxide dismutase. Notably, GLRX2 abrogated LPS-evoked transcripts and releases of pro-inflammatory cytokine (TNF-α, IL-6, and IL-1β), chemokine MCP-1 and adhesion molecule ICAM-1 expression. Furthermore, the activation of Nrf2/HO-1 signaling was demonstrated in LPS-stimulated HUVECs. Importantly, blockage of the Nrf2 pathway counteracted the protective roles of GLRX2 in LPS-triggered endothelial cell injury, oxidative stress and inflammatory response. Thus, these data reveal that GLRX2 may alleviate the progression of atherosclerosis by regulating vascular endothelial dysfunction and inflammation via the activation of the Nrf2 signaling, supporting a promising therapeutic approach for atherosclerosis and its complications. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a prevalent contaminant in feed and food, posing a serious threat to the health of both humans and animals. The pig stands as an ideal subject for the study of DON due to its recognition as the most susceptible animal to DON. In this study, the IPEC-J2 cells were utilized as an in vitro model to explore the potential of SeMet in alleviating the intestinal toxicity and oxidative injury in intestinal epithelial cells when exposed to DON. Cells were treated either with or without 4.0 μM SeMet, in combination with or without a simultaneous treatment with 0.5 μg/mL DON, for a duration of 24 h. Then, cells or related samples were analyzed for cell proliferation, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, gene expressions, and protein expressions. The results showed that SeMet mitigated the cellular toxicity caused by DON, evidenced by elevated cell proliferation and the reduced LDH release of IPEC-J2 cells in the SeMet + DON group vs. the DON group. Moreover, the SeMet treatment markedly promoted antioxidant functions and decreased the oxidative injury in IPEC-J2 cell, which is indicated by the decreased ROS level and up-regulated mRNA levels of GPX1, TXNRD1, Nrf2, and GCLC in IPEC-J2 cells in the SeMet + DON group vs. the DON group. However, in both the absence and presence of exposure to DON, the SeMet treatment did not affect the protein expression of MAPK (JNK, Erk1/2, and P38) and phosphorylated MAPK (p-JNK, p-Erk1/2, and p-P38) in IPEC-J2 cells. Collectively, SeMet alleviated the DON-induced oxidative injury in porcine intestinal epithelial cells independent of the MAPK pathway regulation. [ABSTRACT FROM AUTHOR]

This research evaluated the impacts of selenomethionine (Se-Met) on hepatic functions, oxidative stress, mitochondrial function, and apoptosis of piglets fed deoxynivalenol (DON)-contaminated diets. Twenty-four piglets were allocated four dietary treatments (n = 6) in a 28-day feeding trial. The four treatments included the control group, which received 0.3 mg/kg of Se (as Se-Met) without DON treatment, and the DON treatment groups received 0, 0.3, or 0.5 mg/kg Se as Se-Met. A dietary addition of 0.5 mg/kg Se improved liver pathology and reduced serum aspartate aminotransferase and lactate dehydrogenase levels in piglets fed DON-contaminated diets. Furthermore, 0.5 mg/kg Se mitigated the oxidative stress and apoptosis of piglets fed DON-contaminated diets, as indicated by the decreased reactive oxygen species level, and the down-regulated mRNA levels of NRF-1, Bax, and CASP9 in the liver. Importantly, 0.5 mg/kg Se enhanced the hepatic antioxidant capacity, as evidenced by increased hepatic total antioxidant capacity, catalase, glutathione peroxidase, and total superoxide dismutase activities, as well as the up-regulated mRNA levels of Nrf2, Gclm, NQO1, SOD1, and GPX1 in the liver. Moreover, 0.5 mg/kg Se down-regulated the p-JNK protein level in the liver of piglets fed DON-contaminated diets. Collectively, Se-Met supplementation mitigated liver dysfunction, oxidative injury, and apoptosis through enhancing antioxidant capacity and inhibiting the JNK MAPK pathway in piglets fed DON-contaminated diets. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effect of dietary lutein on semen quality, reproductive hormone profiles, and oxidative injury products in aged roosters. A total of 120 Arbor Acres broiler breeder roosters at 60 weeks of age were randomly distributed into 4 different feeding groups with 6 replicates of 5 roosters each. The four diets contained lutein at 0 (CON), 25 (L1), 50 (L2) and 75 (L3) mg/kg of feed. The feeding trial lasted 4 weeks after one week of adaptation. Results showed that compared to CON, dietary lutein increased (P ≤ 0.001) semen volume, sperm density and viability, and decreased (P ≤ 0.019) sperm abnormality. Here L3 was more pronounced (P < 0.05) on viability and abnormality than other lutein groups. Lutein increased (P ≤ 0.001) serum reproductive hormones including testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEA-S), dihydrotestosterone (DHT), and androstenedione, with L3 showing the best effect on LH, DHT, and DHEA-S. Dietary lutein also increased (P < 0.001) serum lutein contents and lowered (P < 0.001) oxidative injury products including malondialdehyde (MDA), protein carbonyl, and 8-hydroxy 2 deoxyguanosine. Furthermore, a linear (P < 0.05) relationship was found between dietary lutein doses on ejaculate volume, viability, LH, DHT and DHEA-S. In conclusion, dietary lutein can enhance semen quality, maintain reproductive hormone levels and reduce oxidative products. Therefore, it can be used as a dietary supplement to improve the fertility of aged roosters. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a severe and often fatal pulmonary disease. Current treatments for ALI and acute respiratory distress syndrome (ARDS) are limited. Natural product metabolites have shown promise as therapeutic alternatives. However, the effects of Licochalcone B (LCB) on ALI are largely unknown. We investigated the effects of LCB on lipopolysaccharide-challenged mice and human pulmonary microvascular endothelial cells. Cell viability, apoptosis, and ROS production were assessed. Lung tissue histopathology and oxidative stress and inflammation markers were evaluated. Protein expression levels were measured. LCB had no cytotoxic effects on cells and increased cell viability. It reduced apoptosis and ROS levels in cells. In mice with ALI, LCB decreased lung tissue weight and improved oxidative stress and inflammation markers. It also enhanced expression levels of Nrf2, HO-1, and NQO1 while reducing Keap1. LCB protects against LPS-induced acute lung injury in cells and mice. The Keap1/Nrf2 pathway may be involved in its protective effects. LCB shows potential as a strategy to alleviate ALI caused by LPS. [ABSTRACT FROM AUTHOR]

Metoprolol, a drug for hypertension and cardiovascular diseases, has become a contaminant of emerging concern because of its frequent detection in various environmental matrices globally. The dwindling in the biodiversity of useful insects owing to increasing presence of environmental chemicals is currently a great interest to the scientific community. In the current research, the toxicological impact of ecologically relevant concentrations of metoprolol at 0, 0.05, 0.1, 0.25, and 0.5 μg/L on Nauphoeta cinerea nymphs following exposure for 42 consecutive days was evaluated. The insects' behavior was analyzed with automated video‐tracking software (ANY‐maze, Stoelting Co, USA) while biochemical assays were done using the midgut, head and fat body. Metoprolol‐exposed nymphs exhibited significant diminutions in the path efficiency, mobility time, distance traveled, body rotation, maximum speed and turn angle cum more episodes, and time of freezing. In addition, the heat maps and track plots confirmed the metoprolol‐mediated wane in the exploratory and locomotor fitness of the insects. Compared with control, metoprolol exposure decreased acetylcholinesterase activity in insects head. Antioxidant enzymes activities and glutathione level were markedly decreased whereas indices of inflammation and oxidative injury to proteins and lipids were significantly increased in head, midgut and fat body of metoprolol‐exposed insects. Taken together, metoprolol exposure induces neurobehavioral insufficiency and oxido‐inflammatory injury in N. cinerea nymphs. These findings suggest the potential health effects of environmental contamination with metoprolol on ecologically and economically important nontarget insects. [ABSTRACT FROM AUTHOR]

To investigate the impact of the ethanoic fractions of Periploca forrestii Schltr. (P. forrestii) in ameliorating the liver injury caused by fluoride ingestion and to explore the potential mechanisms. Initially, an in vitro fluorosis cell model was constructed using the human normal liver cell line (L-02) induced by fluoride. Cell viability was assessed using the CCK-8 assay kit. The lactate dehydrogenase (LDH) assay kit was utilized to measure LDH content in the cell supernatant, while the malonic dialdehyde (MDA) assay kit was employed to determine MDA levels within the cells. Subsequently, a fluorosis rat model was established, and LDH content in the cell supernatant was measured using the LDH assay kit. Various parameters, including MDA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and reactive oxygen species (ROS) content within the cells, were detected using appropriate assay kits. Additionally, cell apoptosis rate was determined using the Annexin V-FITC/PI cell apoptosis assay kit. The protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Cleaved Caspase-3, Caspase-9, and Cleaved Caspase-9 were analyzed through Western blotting. Compared to the model group, the ethanolic fraction D of P.forrestii (Fr.D) increased cell viability (P

The small intestine is important to the digestion and absorption of rumen undegradable nutrients, as well as the barrier functionality and immunological responses in ruminants. Oxidative stress induces a spectrum of pathophysiological symptoms and nutritional deficits, causing various gastrointestinal ailments. Previous studies have shown that nicotinamide (NAM) has antioxidant properties, but the potential mechanism has not been elucidated. The aim of this study was to explore the effects of NAM on hydrogen peroxide (H2O2)-induced oxidative injury in bovine intestinal epithelial cells (BIECs) and its potential mechanism. The results showed that NAM increased the cell viability and total antioxidant capacity (T-AOC) and decreased the release of lactate dehydrogenase (LDH) in BIECs challenged by H2O2. The NAM exhibited increased expression of catalase, superoxide dismutase 2, and tight junction proteins. The expression of autophagy-related proteins was increased in BIECs challenged by H2O2, and NAM significantly decreased the expression of autophagy-related proteins. When an autophagy-specific inhibitor was used, the oxidative injury in BIECs was not alleviated by NAM, and the T-AOC and the release of LDH were not affected. Collectively, these results indicated that NAM could alleviate oxidative injury in BIECs by enhancing antioxidant capacity and increasing the expression of tight junction proteins, and autophagy played a crucial role in the alleviation.

Abstract Background Zataria multiflora and carvacrol showed various pharmacological properties including anti‐inflammatory and anti‐oxidant effects. However, up to now no studies have explored its potential benefits in ameliorating sepsis‐induced aortic and cardiac injury. Thus, this study aimed to investigate the effects of Z. multiflora and carvacrol on nitric oxide (NO) and oxidative stress indicators in lipopolysaccharide (LPS)‐induced aortic and cardiac injury. Methods Adult male Wistar rats were assigned to: Control, lipopolysaccharide (LPS) (1 mg/kg, intraperitoneal (i.p.)), and Z. multiflora hydro‐ethanolic extract (ZME, 50–200 mg/kg, oral)‐ and carvacrol (25–100 mg/kg, oral)‐treated groups. LPS was injected daily for 14 days. Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration. At the end of the study, the levels of malondialdehyde (MDA), NO, thiols, and antioxidant enzymes were evaluated. Results Our findings showed a significant reduction in the levels of superoxide dismutase (SOD), catalase (CAT), and thiols in the LPS group, which were restored by ZME and carvacrol. Furthermore, ZME and carvacrol decreased MDA and NO in cardiac and aortic tissues of LPS‐injected rats. Conclusions The results suggest protective effects of ZME and carvacrol on LPS‐induced cardiovascular injury via improved redox hemostasis and attenuated NO production. However, additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.

ABSTRACTBackground Acute lung injury (ALI) is a severe and often fatal pulmonary disease. Current treatments for ALI and acute respiratory distress syndrome (ARDS) are limited. Natural product metabolites have shown promise as therapeutic alternatives. However, the effects of Licochalcone B (LCB) on ALI are largely unknown.Methods We investigated the effects of LCB on lipopolysaccharide-challenged mice and human pulmonary microvascular endothelial cells. Cell viability, apoptosis, and ROS production were assessed. Lung tissue histopathology and oxidative stress and inflammation markers were evaluated. Protein expression levels were measured.Results LCB had no cytotoxic effects on cells and increased cell viability. It reduced apoptosis and ROS levels in cells. In mice with ALI, LCB decreased lung tissue weight and improved oxidative stress and inflammation markers. It also enhanced expression levels of Nrf2, HO-1, and NQO1 while reducing Keap1.Conclusion LCB protects against LPS-induced acute lung injury in cells and mice. The Keap1/Nrf2 pathway may be involved in its protective effects. LCB shows potential as a strategy to alleviate ALI caused by LPS.

The use of coumarin (COU) to alleviate the phytotoxic effects of salinity has great potential in improving the phytoremediation of saline and alkaline soils. 30-day bitter gourd plants were exposed to 15 dS m‒1 salinity of neutral (NaCl and Na2SO4) and alkaline (Na2CO3 and NaHCO3) salts. 60-day plants were harvested to record different growth, physiological and biochemical attributes. Salinity significantly subsided plant growth, chlorophyll, photosynthesis, and nutrient acquisition. Salinity induced notable oxidative damage in plants that displayed higher relative membrane permeability (RMP), accumulated elevated ROS (H2O2 and O2•‒) and MDA levels alongside intensified lipoxygenase (LOX) activity. The production of cytotoxic methylglyoxal was also significantly higher in plants under salinity. COU seed priming (50, 100 and 150 mg L‒1) promoted plant growth by circumventing oxidative injury and intensifying oxidative defense. Further, COU maintained the intricate balance between reduced (GSH) and oxidized (GSSG) glutathione to diminish ion excess toxicity, thereby facilitating the phytoremediation of saline soils. The lower doses of COU promoted methylglyoxal and ROS detoxification systems that, in turn, lessened the phytotoxic effects of salinity. COU restored ions homeostasis by augmenting osmotic adjustment in plants under salinity. [ABSTRACT FROM AUTHOR]

Elderly patients (age > 75) sustain larger infarcts with greater mortality from ST elevation myocardial infarcts (STEMI) despite successful reperfusion treatment. Elderly age remains an independent risk despite correction for clinical and angiographic variables. The elderly represent a high-risk population and may benefit from treatment in addition to reperfusion alone. We hypothesized that modulation of cardiac signaling and metabolism with acute, high dose metformin given at reperfusion would exhibit additional cardioprotection. Using a translational aging murine model (22-24-month C57BL/6J mice) of in vivo STEMI (45 min artery occlusion with reperfusion for 24 hours); treatment acutely at reperfusion by high dose metformin decreased infarct size and enhanced contractile recovery, demonstrating cardioprotection in the high-risk aging heart. [ABSTRACT FROM AUTHOR]

To explore the protective function and molecular mechanism of tribuloside in hydrogen peroxide-induced apoptosis and oxidative damage of human lens epithelial cells. Cells were divided into control group, hydrogen peroxide group, hydrogen peroxide+tribuloside 1 µg/ml group, hydrogen peroxide+tribuloside 3 µg/ml group, hydrogen peroxide+tribuloside 10 µg/ml group, hydrogen peroxide+microRNA-NC group, hydrogen peroxide+microRNA-335-3p group, hydrogen peroxide+tribuloside+anti-microRNA-335-3p group. Cell counting kit-8 method and flow cytometry were applied for determining cell viability and apoptosis. Malondialdehyde level, catalase and superoxide dismutase activities were determined using kits. Reverse transcription-quantitative polymerase chain reaction was used for microRNA-335-3p quantification. Kriippellike factor 6 expression was examined via Western blot. Target regulation relationship of miR-335-3p and Kriippel-like factor 6 was analyzed via dual-luciferase report assay. Contrasted with the control group, cell viability, catalase and superoxide dismutase viabilities, and microRNA-335-3p expression were significantly reduced in hydrogen peroxide group (p<0.05), while apoptosis, malondialdehyde and Kriippel-like factor 6 levels were overtly promoted (p<0.05). Contrasted to hydrogen peroxide group, cell viability, catalase and superoxide dismutase activities, and microRNA-335-3p expression in hydrogen peroxide+tribuloside 1 µg/ml group, hydrogen peroxide+tribuloside 3 µg/ml group, hydrogen peroxide+tribuloside 10 µg/ml group were obviously enhanced (p<0.05), but cell apoptosis, malondialdehyde level and Kriippel-like factor 6 protein level were suppressed (p<0.05). Relative to hydrogen peroxide+microRNA-NC group, cell viability, catalase and superoxide dismutase activities in hydrogen peroxide+microRNA-335-3p group were markedly elevated (p<0.05), whereas apoptosis inhibition, malondialdehyde level reduction and Kriippel-like factor 6 protein down-regulation were induced (p<0.05). Compared with hydrogen peroxide+tribuloside group, cell viability, catalase and superoxide dismutase activities in hydrogen peroxide+tribuloside+anti-microRNA-335-3p group were signally inhibited (p<0.05), but apoptosis, malondialdehyde and Kriippel-like factor 6 levels were accelerated (p<0.05). MicroRNA-335-3p directly interacted with Kriippel-like factor 6. Tribuloside could attenuate apoptosis and oxidative damage in hydrogen peroxide-induced cataract model, which was related to microRNA-335-3p/Kriippel-like factor 6 axis. [ABSTRACT FROM AUTHOR]

Abiotic stresses pose significant threat to horticultural crop production worldwide. These stresses adversely affect plant growth, development, and ultimately declined crop growth, yield and quality. In recent years, plant scientists have been actively investigating innovative strategies to enhance abiotic stress resilience in crops, and one promising avenue of research focuses on the use of brassinosteroids (BRs). BRs are a class of plant hormones that play crucial roles in various physiological processes, including cell elongation, differentiation, and stress responses. They have emerged as potent regulators of plant growth and development, and their role in improving abiotic stress tolerance is gaining considerable attention. BRs have been shown to mitigate the negative effects of abiotic stresses by modulating key physiological and biochemical processes, including stomatal regulation, antioxidant defense, osmotic adjustment, and nutrient uptake. Abiotic stresses disrupt numerous physiological functions and lead to undesirable phenotypic traits in plants. The use of BRs as a tool to improve crop resilience offers significant promise for sustainable agriculture in the face of increasing abiotic stresses caused by climate change. By unraveling the phenomenon of BRs, this review emphasizes the potential of BRs as an innovative approach for boosting abiotic stress tolerance and improving the overall productivity and quality of horticultural crops. Further research and field trials are necessary to fully harness the benefits of BRs and translate these findings into practical applications for crop production systems. [ABSTRACT FROM AUTHOR]

Ischemia and reperfusion (IR) damage organs and contribute to many disease states. Few effective treatments exist that attenuate IR injury. The augmentation of nitric oxide (NO) signaling remains a promising therapeutic target for IR injury. NO binds to soluble guanylyl cyclase (sGC) to regulate vasodilation, maintain endothelial barrier integrity, and modulate inflammation through the production of cyclic-GMP in vascular smooth muscle. Pharmacologic sGC stimulators and activators have recently been developed. In preclinical studies, sGC stimulators, which augment the reduced form of sGC, and activators, which activate the oxidized non-NO binding form of sGC, increase vasodilation and decrease cardiac, cerebral, renal, pulmonary, and hepatic injury following IR. These effects may be a result of the improved regulation of perfusion and decreased oxidative injury during IR. sGC stimulators are now used clinically to treat some chronic conditions such as heart failure and pulmonary hypertension. Clinical trials of sGC activators have been terminated secondary to adverse side effects including hypotension. Additional clinical studies to investigate the effects of sGC stimulation and activation during acute conditions, such as IR, are warranted. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a prevalent contaminant in feed and food, posing a serious threat to the health of both humans and animals. The pig stands as an ideal subject for the study of DON due to its recognition as the most susceptible animal to DON. In this study, the IPEC-J2 cells were utilized as an in vitro model to explore the potential of SeMet in alleviating the intestinal toxicity and oxidative injury in intestinal epithelial cells when exposed to DON. Cells were treated either with or without 4.0 μM SeMet, in combination with or without a simultaneous treatment with 0.5 μg/mL DON, for a duration of 24 h. Then, cells or related samples were analyzed for cell proliferation, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, gene expressions, and protein expressions. The results showed that SeMet mitigated the cellular toxicity caused by DON, evidenced by elevated cell proliferation and the reduced LDH release of IPEC-J2 cells in the SeMet + DON group vs. the DON group. Moreover, the SeMet treatment markedly promoted antioxidant functions and decreased the oxidative injury in IPEC-J2 cell, which is indicated by the decreased ROS level and up-regulated mRNA levels of GPX1, TXNRD1, Nrf2, and GCLC in IPEC-J2 cells in the SeMet + DON group vs. the DON group. However, in both the absence and presence of exposure to DON, the SeMet treatment did not affect the protein expression of MAPK (JNK, Erk1/2, and P38) and phosphorylated MAPK (p-JNK, p-Erk1/2, and p-P38) in IPEC-J2 cells. Collectively, SeMet alleviated the DON-induced oxidative injury in porcine intestinal epithelial cells independent of the MAPK pathway regulation.

This research evaluated the impacts of selenomethionine (Se-Met) on hepatic functions, oxidative stress, mitochondrial function, and apoptosis of piglets fed deoxynivalenol (DON)-contaminated diets. Twenty-four piglets were allocated four dietary treatments (n = 6) in a 28-day feeding trial. The four treatments included the control group, which received 0.3 mg/kg of Se (as Se-Met) without DON treatment, and the DON treatment groups received 0, 0.3, or 0.5 mg/kg Se as Se-Met. A dietary addition of 0.5 mg/kg Se improved liver pathology and reduced serum aspartate aminotransferase and lactate dehydrogenase levels in piglets fed DON-contaminated diets. Furthermore, 0.5 mg/kg Se mitigated the oxidative stress and apoptosis of piglets fed DON-contaminated diets, as indicated by the decreased reactive oxygen species level, and the down-regulated mRNA levels of NRF-1, Bax, and CASP9 in the liver. Importantly, 0.5 mg/kg Se enhanced the hepatic antioxidant capacity, as evidenced by increased hepatic total antioxidant capacity, catalase, glutathione peroxidase, and total superoxide dismutase activities, as well as the up-regulated mRNA levels of Nrf2, Gclm, NQO1, SOD1, and GPX1 in the liver. Moreover, 0.5 mg/kg Se down-regulated the p-JNK protein level in the liver of piglets fed DON-contaminated diets. Collectively, Se-Met supplementation mitigated liver dysfunction, oxidative injury, and apoptosis through enhancing antioxidant capacity and inhibiting the JNK MAPK pathway in piglets fed DON-contaminated diets.

Background: The novel peptide neuropeptide W (NPW) was originally shown to function in the control of feeding behavior and energy homeostasis. The aim of this study was to elucidate the putative preventive and therapeutic effects of NPW on colitis-associated oxidative injury and the underlying mechanisms for its action. Methods: Sprague–Dawley rats in the acute colitis groups received NPW (0.5, 1 or 5 µg/kg/day) injections prior to induction of colitis with acetic acid, while the chronic colitis groups were treated after the induction of colitis. In both acute and chronic colitis (CC) groups, treatments were continued for 5 days and the rats were decapitated at the 24th hour of the last injections and colon tissues were collected for assessments. Results: NPW pretreatment given for 5 days before colitis induction, as well as treating rats with NPW during the 5-day course of CC, abolished colonic lipid peroxidation. NPW treatment prevented colitis-induced reduction in blood flow, diminished neutrophil infiltration, and pro-inflammatory cytokine responses. NPW pretreatment only at the higher dose reduced colonic edema and microscopic score and preserved colonic glutathione stores. Elevations in cyclooxygenase (COX) enzyme activity and COX-1 protein level during the acute phase of colitis as well as reduction in COX-2 were all reversed with NPW pretreatment. In contrast, NPW treatment was effective in reducing the elevated COX-2 concentration during the chronic phase. Conclusions: NPW alleviates acetic acid-induced oxidative colonic injury in rats through the upregulation of colonic blood flow as well as the inhibition of COX-2 protein expression and pro-inflammatory cytokine production. [ABSTRACT FROM AUTHOR]

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Abstract Background Soil salt stress is a problem in the world, which turns into one of the main limiting factors hindering maize production. Salinity significantly affects root physiological processes in maize plants. There are few studies, however, that analyses the response of maize to salt stress in terms of the development of root anatomy and respiration. Results We found that the leaf relative water content, photosynthetic characteristics, and catalase activity exhibited a significantly decrease of salt stress treatments. However, salt stress treatments caused the superoxide dismutase activity, peroxidase activity, malondialdehyde content, Na+ uptake and translocation rate to be higher than that of control treatments. The detrimental effect of salt stress on YY7 variety was more pronounced than that of JNY658. Under salt stress, the number of root cortical aerenchyma in salt-tolerant JNY658 plants was significantly higher than that of control, as well as a larger cortical cell size and a lower root cortical cell file number, all of which help to maintain higher biomass. The total respiration rate of two varieties exposed to salt stress was lower than that of control treatment, while the alternate oxidative respiration rate was higher, and the root response of JNY658 plants was significant. Under salt stress, the roots net Na+ and K+ efflux rates of two varieties were higher than those of the control treatment, where the strength of net Na+ efflux rate from the roots of JNY658 plants and the net K+ efflux rate from roots of YY7 plants was remarkable. The increase in efflux rates reduced the Na+ toxicity of the root and helped to maintain its ion balance. Conclusion These results demonstrated that salt-tolerant maize varieties incur a relatively low metabolic cost required to establish a higher root cortical aerenchyma, larger cortical cell size and lower root cortical cell file number, significantly reduced the total respiration rate, and that it also increased the alternate oxidative respiration rate, thereby counteracting the detrimental effect of oxidative damage on root respiration of root growth. In addition, Na+ uptake on the root surface decreased, the translocation of Na+ to the rest of the plant was constrained and the level of Na+ accumulation in leaves significantly reduced under salt stress, thus preempting salt-stress induced impediments to the formation of shoot biomass.

Objective: To investigate the protective effect of astragaloside Ⅳ (AS- Ⅳ) on the lipopolysaccharide (LPS)-induced oxidative injury of osteoblasts precursor cells MC3T3-E1, and to clarify its related mechanism. Methods: The MC3T3-E1 cells in logarithmic growth phase were divided into control group, LPS group and different concentrations (10，25，50 and 100 mg·L-1) of AS- Ⅳ groups. CCK-8 method was used to detect the cell activities in various groups. The MC3T3-E1 cells in logarithmic growth phase were divided into control group, LPS group, AS- Ⅳ group, AS- Ⅳ +LY294002 ［phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway inhibitor］group. Flow cytometry was used to detect the levels of reactive oxygen species (ROS) in the cells in various groups. The levels of malondialdehyde (MDA) and glutathione (GSH) and the activities of superoxide dismutase (SOD) in the cells in various groups were determined with the related kits. The expression levels of heme oxygenase (HO-1) mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR (RT-qPCR) method. Western blotting method was used to detect the expression levels of PI3K，phosphorylated Akt (p-Akt)，and nuclear factor-E2 related factor 2 (Nrf2)，B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) in the cells in various groups. Results: The CCK-8 method results showed that compared with control group, the cell activity in LPS group was significantly decreased (P<0. 01)； compared with LPS group, the activities of cells in 50 and 100 mg·L-1 AS- Ⅳ groups were significantly increased (P<0. 01). Compared with control group, the ROS and MDA levels in the cells in LPS group were significantly increased (P<0. 01), while the SOD activity and GSH level were decreased (P<0. 01)； compared with LPS group, the ROS and MDA levels in the cells in AS- Ⅳ group were significantly decreased (P<0. 01), the SOD activity and GSH level were significantly increased (P< 0. 01)； compared with AS-Ⅳ group, the ROS and MDA levels in the cells in AS-Ⅳ +LY294002 group were significantly increased ( P<0. 01), the SOD activity and GSH level were significantly decreased ( P< 0. 01). Compared with control group, the expression level of HO-1 mRNA and the expression levels of p-Akt, Nrf2, HO-1, and Bcl-2 proteins in the cells in LPS group were significantly decreased (P<0. 01), while the expression level of Bax protein was significantly increased (P<0. 01)； compared with LPS group, the expression level of HO-1 mRNA and the expression levels of p-Akt, Nrf2, HO-1，and Bcl-2 proteins in the cells in AS- Ⅳ group were signicantly increased (P<0. 01), while the expression level of Bax protein was significantly decreased (P<0. 01)；compared with AS- Ⅳ group, the expression level of HO-1 mRNA and the expression levels of p-Akt，Nrf2 HO-1 and Bcl-2 proteins in the cells in AS- Ⅳ + LY294002 group were significantly decreased (P<0. 01)，and the expression level of Bax protein was significantly increased (P<0. 01). Conclusion：AS- Ⅳ can play protective effect on the LPS-induced osteoblast injury by mediating PI3K/Akt/Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

The inhibition of intimal hyperplasia (IH) is an effective strategy to improve the long-term outcome of endovascular therapy and prevent restenosis. Farrerol, a naturally occurring dihydroflavone with a variety of bioactivities, exerts inhibitory effects against balloon injury-induced IH in rats. In the present study, bioinformatics analysis, in combination with in vitro experimental validation, was performed to elucidate the underlying inhibitory mechanisms. The protein–protein interaction (PPI) network was assessed to identify farrerol-related protein targets in the context of IH, based on which biological functions and pathway enrichment were analyzed. The proliferation and cell cycle distribution of vascular smooth muscle cells (VSMCs) were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H -tetrazolium bromide and 5-ethynyl-2-deoxyuridine incorporation assays and flow cytometric analysis, respectively. The level of pro-inflammatory cytokines in the cell culture medium was estimated using an enzyme-linked immunosorbent assay (ELISA). Protein expression in A7r5 cells was determined by western blotting. Forty-six IH-related targets of farrerol were identified, and the PI3K/Akt/mTOR pathway was highly enriched among the 43 predicted pathways (P <.05). In serum (10% fetal bovine serum)-induced A7r5 cells, farrerol inhibited proliferation through non-cytotoxic effects, induced cell cycle arrest in the G0/G1 phase, and suppressed the activation of the PI3K/Akt/mTOR pathway. In H2O2 (300 µM)-induced A7r5 cells, farrerol reduced the release of IL-1 β and TNF- α and reversed the suppressive effect on the PI3K/Akt/mTOR pathway in response to H2O2 stimulation. In conclusion, farrerol inhibits the proliferation of VSMCs and protects VSMCs from oxidative injury via the bidirectional modulation of the PI3K/Akt/mTOR signaling pathway, which might contribute to the suppression of neointima formation. [ABSTRACT FROM AUTHOR]

Sulforaphane (SFN), a bioactive phytocompound extracted from cruciferous plants, has received increasing attention due to its vital cytoprotective role in eliminating oxidative free radical through activation of nuclear factor erythroid 2-related factor (Nrf2)-mediated signal transduction pathway. This study aims at a better insight into the protective benefit of SFN in attenuating paraquat (PQ)-caused impairment in bovine in vitro-matured oocytes and the possible mechanisms involved therein. Results showed that addition of 1 μM SFN during oocyte maturation obtained higher proportions of matured oocytes and in vitro-fertilized embryos. SFN application attenuated the toxicological effects of PQ on bovine oocytes, as manifested by enhanced extending capability of cumulus cell and increased extrusion proportion of first polar body. Following incubation with SFN, oocytes exposed to PQ exhibited reduced intracellular ROS and lipid accumulation levels, and elevated T-SOD and GSH contents. SFN also effectively inhibited PQ-mediated increase in BAX and CASPASE-3 protein expressions. Besides, SFN promoted the transcription of NRF2 and its downstream antioxidative-related genes GCLC, GCLM, HO-1, NQO-1, and TXN1 in a PQ-exposed environment, indicating that SFN prevents PQ-caused cytotoxicity through activation of Nrf2 signal transduction pathway. The mechanisms underlying the role of SFN against PQ-induced injury included the inhibition of TXNIP protein and restoration of the global O-GlcNAc level. Collectively, these findings provide novel evidence for the protective role of SFN in alleviating PQ-caused injury, and suggest that SFN application may be an efficacious intervention strategy against PQ cytotoxicity.

Background: Oxidative stress has been shown to be an important factor, which plays a significant role in the pathogenesis of neurodegenerative disorders. Heat Shock Protein-27 (HSP-27) has been implicated in antioxidant responses against oxidative stress. Trehalose is a natural disaccharide widely used in a variety of food products with demonstrated protective effects against several neurodegenerative diseases. This study investigated the effects of trehalose on antioxidant responses, and the gene expressions for HSP-27 and caspase-3 against hydrogen peroxide (H2O2) induced oxidative injury in PC-12 cell line. Methods: The PC-12 cells were treated with various concentrations of H2O2 and trehalose for 24hr. The cell viability was assessed, using MTT and Lactate Dehydrogenase (LDH) release assays. Moreover, the activity of Catalase (CAT) and Glutathione Peroxidase (GPx) enzymes, and the Malondialdehyde (MDA) levels were determined. In addition, the levels of HSP-27 and caspase-3 gene expressions were measured. Results: The results indicated that the pretreatment with trehalose increased cell survival against the H2O2-induced oxidative injury. Furthermore, trehalose elevated the CAT and GPx activities and reduced MDA levels compared to that of control group (P˂0.05). Moreover, trehalose upregulated the HSP-27 gene expression, while reducing the expression of caspase-3 gene compared to that of the untreated cells (P˂0.05). All of these biochemical changes were found to be dose-dependent for trehalose. Conclusion: Based on the study findings, trehalose had the capacity to attenuate the oxidative stress and cell injury. Therefore, trehalose may be suggested as a therapeutic agent to treat neurodegenerative disorders caused by oxidative stress damages.

Background: Soil salt stress is a problem in the world, which turns into one of the main limiting factors hindering maize production. Salinity significantly affects root physiological processes in maize plants. There are few studies, however, that analyses the response of maize to salt stress in terms of the development of root anatomy and respiration. Results: We found that the leaf relative water content, photosynthetic characteristics, and catalase activity exhibited a significantly decrease of salt stress treatments. However, salt stress treatments caused the superoxide dismutase activity, peroxidase activity, malondialdehyde content, Na+ uptake and translocation rate to be higher than that of control treatments. The detrimental effect of salt stress on YY7 variety was more pronounced than that of JNY658. Under salt stress, the number of root cortical aerenchyma in salt-tolerant JNY658 plants was significantly higher than that of control, as well as a larger cortical cell size and a lower root cortical cell file number, all of which help to maintain higher biomass. The total respiration rate of two varieties exposed to salt stress was lower than that of control treatment, while the alternate oxidative respiration rate was higher, and the root response of JNY658 plants was significant. Under salt stress, the roots net Na+ and K+ efflux rates of two varieties were higher than those of the control treatment, where the strength of net Na+ efflux rate from the roots of JNY658 plants and the net K+ efflux rate from roots of YY7 plants was remarkable. The increase in efflux rates reduced the Na+ toxicity of the root and helped to maintain its ion balance. Conclusion: These results demonstrated that salt-tolerant maize varieties incur a relatively low metabolic cost required to establish a higher root cortical aerenchyma, larger cortical cell size and lower root cortical cell file number, significantly reduced the total respiration rate, and that it also increased the alternate oxidative respiration rate, thereby counteracting the detrimental effect of oxidative damage on root respiration of root growth. In addition, Na+ uptake on the root surface decreased, the translocation of Na+ to the rest of the plant was constrained and the level of Na+ accumulation in leaves significantly reduced under salt stress, thus preempting salt-stress induced impediments to the formation of shoot biomass. [ABSTRACT FROM AUTHOR]

More research is required to understand how melatonin protects neurons. The study aimed to find out if and how long non-coding RNA (lncRNA) contributes to melatonin's ability to defend the hippocampus from H2O2-induced oxidative injury. LncRNAs related to oxidative injury were predicted by bioinformatics methods. Mouse hippocampus-derived neuronal HT22 cells were treated with H2O2 with or without melatonin. Viability and apoptosis were detected by Cell Counting Kit-8 and Hoechst33258. RNA and protein levels were measured by quantitative real-time PCR, Western blot, and immunofluorescence. Bioinformatics predicted that 38 lncRNAs were associated with oxidative injury in mouse neurons. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was related to H2O2-induced oxidative injury and up-regulated by melatonin in HT22 cells. The knockdown of NEAT1 exacerbated H2O2-induced oxidative injury, weakened the moderating effect of melatonin, and abolished the increasing effect of melatonin on the mRNA and protein level of Slc38a2. Taken together, melatonin attenuates H2O2-induced oxidative injury by upregulating lncRNA NEAT1, which is essential for melatonin stabilizing the mRNA and protein level of Slc38a2 for the survival of HT22 cells. The research may assist in the treatment of oxidative injury-induced hippocampal degeneration associated with aging using melatonin and its target lncRNA NEAT1. [ABSTRACT FROM AUTHOR]

Menadione sodium bisulphite (MSB) is known to augment plant defense responses against abiotic and biotic stresses. Wheat is an essential cereal with significant sensitivity to alkaline stress. The present study investigated the effects of MSB seed priming (5 and 10 mM) in alleviating the damaging effects of alkaline stress on hydroponically grown wheat cultivars (salt-sensitive cv. MH-97 and salt-tolerant cv. Millat-2011). Our findings revealed a significant reduction in growth, chlorophyll contents, total soluble proteins, free amino acids, K+, Ca2+, P, and K+/Na+ in wheat cultivars under alkaline stress. In contrast, a noteworthy accretion in lipid peroxidation, H2O2 production, proline levels, antioxidant enzyme activities, soluble sugars, antioxidant compounds, and Na+ levels was noticed in wheat plants grown in alkaline hydroponic medium. MSB priming significantly lowered chlorophyll degradation, Na+ levels, and osmolyte accumulation. Further, K+/Na+ ratio, antioxidant compounds, and antioxidant enzyme activities were higher in plants primed with MSB. Therefore, seed priming eminently protected plants by regulating osmotic adjustment and strengthening oxidative defense under alkaline stress. Plants administered 5 mM MSB as seed priming manifested better tolerance to alkaline stress. [ABSTRACT FROM AUTHOR]

Objective: To investigate the antioxidative and antidiabetic effects of Harpephyllum caffrum bark infusion as well as its effects on glucogenic and nucleotide hydrolyzing enzyme activities in FeSO4- induced oxidative stress in rat hepatic tissue. Methods: Harpephyllum caffrum infusion was prepared from dried plant materials (40 g) infused in boiling water (400 mL) for 20 min at room temperature. The antioxidative and inhibitory activities against carbohydrate digestive enzymes of the infusion were determined using established protocols. The liver tissues of rats were used for glucose uptake assay and to evaluate the infusion’s effect on endogenous antioxidant, glucogenic, and nucleotide hydrolyzing enzyme activities in FeSO4-induced hepatic injury. Results: The Harpephyllum caffrum infusion significantly reduced ferric iron (FRAP) and free radicals (OH• and DPPH) in a dose- dependent manner. It inhibited α-amylase and α-glucosidase activities and increased glucose uptake in hepatic tissues. FeSO4 significantly decreased glutathione concentration, catalase, and superoxide dismutase activities while increasing malondialdehyde level, glycogen phosphorylase, fructose-1,6-bisphosphatase, and adenosine triphosphatase activities. However, treatment with Harpephyllum caffrum infusion reversed FeSO4-induced changes. Characterization of the infusion revealed the presence of catechol, O-pyrocatechuic acid, mequinol, maltol, and glycoside derivatives. Conclusions: The Harpephyllum caffrum infusion demonstrates antidiabetic and antioxidative potentials in in vitro models of type 2 diabetes as depicted by its ability to inhibit carbohydrate digestive enzymes, mitigate oxidative imbalance, and regulate glucogenic and nucleotide hydrolyzing enzyme activities in oxidative hepatic injury.

Nickel is a common heavy metal pollutant in industrial areas and can cause oxidative damage to human and animal organs. As an essential amino acid with antioxidant function, methionine (Met) may protect the body from the oxidative stress induce by nickel, however, there is not enough research to study in this aspect. The study aims at investigating the effect of Met on the nickel-induced intestinal oxidative stress and further detected the gut microbiota changes. Mice were gavaged with quantitative NiCl2 (1.6 mg/ml, 0.25 ml) and fed with different doses of methionine in each group. The contents of intestinal oxidation product and antioxidant enzymes were determined by different biochemical quantitative methods, and the data showed that NiCl2 increased the content of intestinal oxidation product (MDA), and the antioxidant enzymes (GSH-Px, GR, SOD and CAT) were decreased. But this situation was alleviated in the group fed with additional methionine solution (0.5 mg/ml). In addition, we detected changes in the gut microbiota using high-throughput sequencing, the results showed that the structure of intestinal flora was disturbed by NiCl2, but methionine restored the germs with antioxidant capacity. Based on the results, we speculate that methionine can alleviate the impact of NiCl2 on the intestinal by enhancing the activity of antioxidant enzymes and the number of gut bacteria with anti-oxidation, suggesting that methionine as a nutritional additive may have the potential to treat nickel poisoning.

Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease associated with extensive mucosal damage. Prodigiosins (PGs) are natural bacterial pigments with well-known antioxidant and immunosuppressive properties. In the current study, we examined the possible protective effect of PGs loaded with selenium nanoparticles (PGs-SeNPs) against acetic acid (AcOH)-induced UC in rats. Thirty-five rats were separated into five equal groups with seven animals/group: control, UC, PGs (300 mg/kg), sodium selenite (Na2SeO3, 2 mg/kg), PGs-SeNPs (0.5 mg/kg), and 5-aminosalicylates (5-ASA, 200 mg/kg). Interestingly, PGs-SeNPs administration lessened colon inflammation and mucosal damage as indicated by inhibiting inflammatory markers upon AcOH injection. Furthermore, PGs-SeNPs improved the colonic antioxidant capacity and prevented oxidative insults as evidenced by the upregulation of Nrf2- and its downstream antioxidants along with the decreased pro-oxidants [reactive oxygen species (ROS), carbonyl protein, malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and nitric oxide (NO] in the colon tissue. Furthermore, PGs-SeNPs protected intestinal cell loss through blockade apoptotic cascade by decreasing pro-apoptotic proteins [Bcl-2-associated X protein (Bax) and caspase-3] and increasing anti-apoptotic protein, B cell lymphoma 2 (Bcl2). Collectively, PGs-SeNPs could be used as an alternative anti-colitic option due to their strong anti-inflammatory, antioxidant, and anti-apoptotic activities. [ABSTRACT FROM AUTHOR]

Age-related cataract (ARC) is one of the leading blinding eye diseases worldwide. Chronic oxidative stress and the apoptosis of human lens epithelial cells (HLECs) have been suggested to be themechanism underlying cataract formation. Acetyl-11-keto-ß-boswellic acid (AKBA) is a pentacyclic triterpene with antioxidative and antiapoptotic effects. In this study, we investigated the potential effects of AKBA on oxidative-induced HLECs injury and cataract formation. H2O2 was used to simulate HLECs oxidative injury in vitro, andNa2SeO3 was applied to establish an in vivo cataract model. In our current study, a cell counting kit-8 (CCK-8) assay was performed to evaluate the effects of H2O2 and AKBA on cell viability in vitro. Intracellular reactive oxygen species (ROS) levels were measured with the ROS assay to verify the antioxidant capacity of AKBA. Apoptotic cells were detected and measured by TUNEL staining and flow cytometry, and quantitative real-time (qRT)-PCR and Western blotting were applied to examine the transcription and expression of apoptosis-related proteins. Furthermore, immunofluorescence staining was performed to locate factor-erythroid 2-related factor 2 (Nrf2), and the protein levels of Nrf2, kelch-like ECH-associated protein 1 (Keap1) and heme oxygenase-1 (HO-1) were determined by Western blotting. Finally, we observed the degree of lens opacity and performed hematoxylin-eosin (H&E) staining to assess the protective effect of AKBA on cataract formation in vivo. AKBA increased HLECs viability under H2O2 stimulation, decreased intracellular ROS levels and alleviated the cell apoptosis rate in vitro. AKBA significantly decreased the expression of caspase-3 and Bax and increased the content of Bcl-2. The results of immunofluorescence and immunohistochemical staining proved that the expression and nuclear translocation of Nrf2 were activated with AKBA treatment in vivo and in vitro. Moreover, computational docking results showed that AKBA could bind specifically to the predicted Keap1/Nrf2 binding sites. After AKBA activation, Nrf2 dissociates from the Nrf2/Keap1 complex, translocates into the nucleus, and subsequently promotes HO-1 expression. In addition, AKBA attenuated lens opacity in selenite-induced cataracts. Overall, these findings indicated that AKBA alleviated oxidative injury and cataract formation by activating the Keap1/Nrf2/HO-1 cascade. Therefore, our current study highlights that AKBA may serve as a promising treatment for ARC progression. [ABSTRACT FROM AUTHOR]

Background: Tephrosia purpurea (TP), commonly known as wild indigo, is traditionally used in treatment of splenomegaly. It is an important ingredient of various Ayurvedic medicines used in treatment of liver diseases. Objectives: Thus, the study was undertaken to investigate the hepatoprotective efficacy of ethanolic extract of TP against Aflatoxin B1 (AFB1) induced liver injury. Materials and Methods: The ethanolic extract of TP was prepared by Soxhlet extraction method. Presence of polyphenols and antioxidant potential were assessed. The antiproliferative activity of extract was tested on HepG2 cells using MTT assay. For in vivo studies female Wistar rats were randomly divided into 6 groups with 6 animals in each. The entire regime was of 33 days. AFB1 was administered at 200 µg/kg dose and TP was administered at three different doses (100, 200 and 300 mg/kg). 24 hr after last treatment the animals were euthanised and liver and blood samples were collected. Results: 45.77± 2.53 µg/ml IC50 of extract was seen on HepG2 cells. A significant elevation in serum transaminases, triglycerides (TG) and LPO was seen after AFB1 intoxication. Whereas decline in activities of GSH, SOD, CAT, G6Pase and ATPase were observed. Treatment with different doses of TP restored its activities towards normal indices. Maximum recovery was seen with 300 mg/kg dose of TP. Conclusion: It may be concluded that TP possess hepatoprotective efficacy against AFB1 induced oxidative injury and it may prove to be of clinical use after further studies. [ABSTRACT FROM AUTHOR]